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Objective: PIK3CA is the most common pathway affected by mutations in breast cancer. PIK3CA/PTEN pathway is under intense investigation as a possible target for molecular therapy. Dysregulation PIK3CA/PTEN pathway is a substantial mechanism for the development of resistance to anti-HER2 therapy. Therefore, we aimed to study the PIK3CA/PTEN in breast cancer patients in Saudi population. Methods: We applied PTEN immunohistochemistry on 98 patients. Then, we applied next-generation sequencing to determine the genetic variations associated with the development of breast cancer and their correlations with clinicopathological variables. Results: PTEN expression was significantly correlated with lymph node metastasis (LNM), tumor stage, lymphovascular invasion (LVI) and triple negative breast cancer (TNBC). The prevalence of the PIK3CA mutation was 33.3% of cases and it was significantly associated with LNM, tumor stage, and with PTEN expression. c-MET mutation was identified in 41.7% of cases and it was associated with tumor stage and with TNBC, while c-KIT mutation was detected in 20.8% of cases, and it was significantly associated with TNBC only. Patients with positive PTEN expression had a significantly better overall survival (OS); on the contrary, patients with PIK3CA and c-MET had a significantly worse OS. Conclusion: Our study confirms the importance of PIK3CA/PTEN pathway in breast cancer patients. A high frequency of PIK3CA and c-MET mutations was detected and was associated with poor prognosis. Both c-MET and c-KIT genes have significant roles in developing TNBC. These findings should be expanded to a larger group study to improve the clinical outcomes and individualizing treatment.

Malignant myoepithelial tumors are a type of recently recognized tumor that occur primarily in soft tissue characterized by myoepithelial elements without ductal differentiation. It appears that this type of tumor may be related to parachordoma or mixed tumor. However, only a small number of cases have been described in the submandibular, parotid and accessory glands, and bone is an extremely rare site for myoepithelial tumor presentation. We herein report a rare case of a 56-year-old woman diagnosed with primary malignant myoepithelial tumor originating in the tibia. Histologically, the tumor was composed of a nodular spindled and epithelioid neoplasm with mild to moderate nuclear pleomorphism embedded within variably collagenous, myxoid and chondromyxoid stroma. Immunohistochemistry staining showed tumor cells that were strongly positive for S100 protein, epithelial membrane antigen, vimentin and focally positive for p63 and cytokeratins (AE1/AE3); they were negative for desmin, smooth muscle actin, HMB45, Melan-A, CD99 and bcl2. This is all consistent with the phenomenon of myoepithelial differentiation. Additionally, Fluorescence in Situ Hybridization (FISH) was shown to be positive for EWSR1 translocation. Ultimately, the final diagnosis was primary myoepithelial carcinoma of bone. The patient was free of disease after three years of follow-up. In this article, we have shared our experience in documenting this rare medical entity, to clarify the crucial need for distinguishing myoepithelial carcinoma from primary benign and malignant bone and cartilage forming tumors. Keywords: Myoepithelial carcinoma, Rare bone tumors

Inhibin and activins are dimeric glycoproteins that are structurally and functionally related to transforming growth factor-β and are composed of 1 α-subunit and 1 of 2 β-subunits (βA or βB). In recent years, there has been controversy about their role in adrenal tumors and their suitability as a diagnostic/predictive marker. Inhibin α and inhibin/activin β protein expression was assessed on 47 adrenal tissue specimens by means of immunohistochemistry. Positive immunoreactivity of inhibin-α was seen in all studied hyperplastic adrenal glands, 90.9% of cortical adenomas, and 83.3% of adrenal cortical carcinomas. In contrast, the adrenomedullary neoplasms had a statistically significantly different behavior (P=0.001). We observed the negative expression of inhibin α in 85% and 80% of benign and malignant pheochromocytomas, respectively. As regards the immunoreactivity of inhibin/activin β, 80% of adrenal hyperplasias, 81.8% of cortical adenomas, and 83.3% of adrenal cortical carcinomas showed positivity. Strong-to-weak positive staining of inhibin/activin β was observed in 70% of benign pheochromocytomas, whereas malignant pheochromocytomas showed positive immunohistochemical staining in 40% of cases with weak intensity. The scoring of inhibin/activin β immunoreactivity between adrenocortical and adrenomeullary neoplasia failed to reach the significant value (P=0.1). Our results demonstrate that inhibin α had a diagnostic role, differentiating between the adrenocortical and adrenomedullary neoplasms. Moreover, inhibin/activin β might play a predictive role for malignant potential in pheochromocytoma. Further studies are warranted to determine whether they play a diagnostic/predictive role in adrenal tumors or are just surrogate markers for this group of neoplasia.